Candidate Gene Analyses of Skeletal Variation in Malocclusion

C S G da Fontoura; S F Miller; G L Wehby; B A Amendt; N E Holton; T E Southard; V Allareddy; L M Moreno Uribe

doi:10.1177/0022034515581643

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Candidate Gene Analyses of Skeletal Variation in Malocclusion

Journal article

Open access

Peer reviewed

Candidate Gene Analyses of Skeletal Variation in Malocclusion

C S G da Fontoura, S F Miller, G L Wehby, B A Amendt, N E Holton, T E Southard, V Allareddy and L M Moreno Uribe

Journal of dental research, Vol.94(7), pp.913-920

07/2015

DOI: 10.1177/0022034515581643

PMCID: PMC4530344

PMID: 25910506

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Abstract

This study evaluated associations between craniofacial candidate genes and skeletal variation in patients with malocclusion. Lateral cephalometric radiographs of 269 untreated adults with skeletal classes I, II, and III malocclusion were digitized with 14 landmarks. Two-dimensional coordinates were analyzed using Procrustes fit and principal component (PC) analysis to generate continuous malocclusion phenotypes. Skeletal class classifications (I, II, or III) were used as a categorical phenotype. Individuals were genotyped for 198 single-nucleotide polymorphisms (SNPs) in 71 craniofacial genes and loci. Phenotype-genotype associations were tested via multivariate linear regression for continuous phenotypes and multinomial logistic regression for skeletal malocclusion class. PC analysis resulted in 4 principal components (PCs) explaining 69% of the total skeletal facial variation. PC1 explained 32.7% of the variation and depicted vertical discrepancies ranging from skeletal deep to open bites. PC1 was associated with a SNP near PAX5 (P = 0.01). PC2 explained 21.7% and captured horizontal maxillomandibular discrepancies. PC2 was associated with SNPs upstream of SNAI3 (P = 0.0002) and MYO1H (P = 0.006). PC3 explained 8.2% and captured variation in ramus height, body length, and anterior cranial base orientation. PC3 was associated with TWIST1 (P = 0.000076). Finally, PC4 explained 6.6% and detected variation in condylar inclination as well as symphysis projection. PC4 was associated with PAX7 (P = 0.007). Furthermore, skeletal class II risk increased relative to class I with the minor alleles of SNPs in FGFR2 (odds ratio [OR] = 2.1, P = 0.004) and declined with SNPs in EDN1 (OR = 0.5, P = 0.007). Conversely, skeletal class III risk increased versus class I with SNPs in FGFR2 (OR 2.2, P = 0.005) and COL1A1 (OR = 2.1, P = 0.008) and declined with SNPs in TBX5 (OR = 0.5, P = 0.014). PAX5, SNAI3, MYO1H, TWIST1, and PAX7 are associated with craniofacial skeletal variation among patients with malocclusion, while FGFR2, EDN1, TBX5, and COL1A1 are associated with type of skeletal malocclusion.

Cephalometry - methods

Humans

Mandible - pathology

Middle Aged

PAX7 Transcription Factor - genetics

Malocclusion, Angle Class III - genetics

Young Adult

Anatomic Landmarks - pathology

Collagen Type I - genetics

Malocclusion, Angle Class II - pathology

Adult

Malocclusion, Angle Class I - pathology

Nuclear Proteins - genetics

Snail Family Transcription Factors

Malocclusion, Angle Class I - genetics

Genetic Association Studies

PAX5 Transcription Factor - genetics

Open Bite - genetics

Genotype

Image Processing, Computer-Assisted - methods

Transcription Factors - genetics

DNA-Binding Proteins - genetics

Overbite - genetics

T-Box Domain Proteins - genetics

Malocclusion, Angle Class III - pathology

Phenotype

Malocclusion, Angle Class II - genetics

Adolescent

Twist-Related Protein 1 - genetics

Myosin Type I

Polymorphism, Single Nucleotide - genetics

Zinc Fingers - genetics

Aged

Receptor, Fibroblast Growth Factor, Type 2 - genetics

Details

Title: Subtitle: Candidate Gene Analyses of Skeletal Variation in Malocclusion
Creators: C S G da Fontoura - Dows Institute for Research, College of Dentistry, University of Iowa, Iowa City, IA, USA
S F Miller - Dows Institute for Research, College of Dentistry, University of Iowa, Iowa City, IA, USA
G L Wehby - Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City, IA, USA
B A Amendt - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
N E Holton - Dows Institute for Research, College of Dentistry, University of Iowa, Iowa City, IA, USA Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, IA, USA
T E Southard - Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, IA, USA
V Allareddy - Department of Oral Pathology-Radiology and Medicine, University of Iowa, Iowa City, IA, USA
L M Moreno Uribe - Dows Institute for Research, College of Dentistry, University of Iowa, Iowa City, IA, USA Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, IA, USA lina-moreno@uiowa.edu
Resource Type: Journal article
Publication Details: Journal of dental research, Vol.94(7), pp.913-920
DOI: 10.1177/0022034515581643
PMID: 25910506
PMCID: PMC4530344
NLM abbreviation: J Dent Res
ISSN: 0022-0345
eISSN: 1544-0591
Publisher: United States
Grant note: R90 DE024296 / NIDCR NIH HHS T90 DE023520 / NIDCR NIH HHS T32-DE014678-09 / NIDCR NIH HHS 2 UL1 TR000442-06 / NCATS NIH HHS UL1 TR000442 / NCATS NIH HHS
Language: English
Date published: 07/2015
Academic Unit: Preventive and Community Dentistry; Radiology; Orthodontics; Anthropology; Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Health Management and Policy; Economics; Craniofacial Anomalies Research Center; Public Policy Center (Archive); Dental Research
Record Identifier: 9984025315902771

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